1. Field
The present invention relates to a composition comprising a turmeric extract for the prevention and treatment of influenza virus infection and the inhibition of neuraminidase activity.
2. Description of Related Art
Influenza virus is one of the most infective viruses that cause acute respiratory diseases, and in severe instances, cause herd infection or pandemic over the world, particularly giving rise to serious respiratory symptoms in children, the aged, patients with cardiopulmonary diseases, and the like (Hien, T. T. et al. N. Eng. J. Med., 350, 1179, 2004). Influenza virus is a genus of the Orthomyxovirus and has three types, that is, A, B, and C. Among them, particularly A and B types routinely spread in people. Influenza virus has eight RNA gene segments, and two glycoproteins, hemagglutinin (HA) and neuraminidase (NA) that are a type of surface antigen found on the surface of the influenza virus. Hemagglutinin is a trimer with a head and a stalk, and the head of the trimer involves a majority of antigenic variation. Hemagglutinin binds to terminal sialic acid residues on the surface of host cells to enable viruses to attach to and enter in the host cells in sequence (Chandrasekaran, A. et al. Nature biotechnology 26, 107, 2008). Neuraminidase is a mushroom-shaped tetramer with a head and a stalk, and the head of the tetramer has active sites on the top surfaces thereof. Neuraminidase cleaves the alpha-ketosidic bond between oligosacchrides at cell surfaces and terminal neuraminic acid residues to assist viruses replicated and proliferated in the infected cells to exit outside the host cells and enter in the respiratory mucosa cells (a. Mark, V. I. Nature review 6, 967, 2007. b. Huberman, K. et al. Virology 214, 294, 1995).
The same subtype of virus surface antigen produces an antigenic variation to generate new antigenic variants every year. Particularly, among influenza viruses, avian influenza virus, which is still a threat undergoes an antigenic shift to infect various kinds of birds such as chickens, turkeys, ducks, wild birds, and the like. Avian influenza virus spreads so quickly that once a chicken is infected, 80% or more of the chickens are killed. Avian influenza virus which poses the most damage and threat to the poultry industry over the world causes viral diseases, and this pervasive effect is not just limited to the poultry industry. It has been reported that avian influenza virus can infect humans, which causes diseases to spread among humans (Gubareva, L. V. et al. Lancet. 355, 2000). In past ages, influenza virus has been known to cause many diseases. Specifically, there have been three flu pandemics in the twentieth century, Spanish flu pandemic (H1N1) which killed about thirty millions, the Asian Flu (H2N2) which killed and an estimated one million and the Hong Kong Flu (H3N2) which also killed an estimated one million. Later, in 2003 to 2008, 385 were infected and 243 died. Recently, the World Health Organization (WHO) officially announced that the novel swine-origin influenza break out of April, 2009 as being pandemic. As of Jun. 29, 2009, 70,893 people (including 311 deaths) in over 115 countries were infected, and a South Korean nun visiting Mexico for volunteer work has been confirmed as the first flu patient on May 2, 2009. As of Aug. 16, 2009, a cumulative number of 2,089 flu patients (including 2 deaths) were reported in South Korea.
To prevent and treat the influenza virus infection, consideration may be made to inhibit the absorption in epithelial cells, the invasion into cells, the transcription or replication of genes, the synthesis of proteins, or the release from cells, each having been the focus of the antiviral studies.
To treat diseases caused by influenza virus, four substances, that is, Amatadine, Rimatadine, Zanamivir, and Oseltamivir have been used with the approval of Food and Drug Administration (FDA). As older M2 inhibitors, Amatadine and Rimatadine have antiviral effects by blocking an ion channel of a membrane protein, particularly M2 protein that is essential to the proliferation of virus to inhibit the uncoating of the virus, but are only effective against influenza A virus. Also, it is reported that the virus becomes more tolerant and resistant to the substances as a consequence of being used over 40 years, and severe side effects occur in the nervous system and stomach (Bantia, S. et al. Antiviral Research 69, 39, 2006). Since 1999, as new drugs to treat virus infection, Zanamivir and Oseltamivir called neuraminidase inhibitors have been used, which play an important role in proliferation of virus, have a low prevalence of tolerance, and are active against both influenza A and B viruses (Zhang, J. et al. Bioorg. Med. Chem. Lett. 16, 3009, 2006).
However, Zanamivir has an advantage of high antiviral effects but is disadvantageous in low bioavailability and quick release from the kidney, and Oseltamivir causes severe vomiting (Ryan, D. M. et al. Antimicrob. Agents Chemother., 39, 2583, 1995).
As mentioned above, existing antivirals have serious side effects and require considerable caution in their application. Also, the development effects of vaccines are low when the vaccine virus is not matched to circulating viruses. Accordingly, there is an increasing need for a new influenza antiviral with excellent infection inhibition and stability.
To satisfy the need, the inventors invented the present invention after discovering that a turmeric extract, its fraction or a curcuminoid-based compound separated therefrom has neuraminidase inhibitory activity, and antiviral and cell degeneration inhibitory effects.